title: Bile carcinoembryonic cell adhesion molecule 6 (CEAM6) as a biomarker of malignant biliary stenoses.
abstract: Differentiating malignant from nonmalignant biliary stenoses is challenging. This could be facilitated by the measurement of cancer biomarkers in bile. We aimed at (i) identifying new cancer biomarkers by comparative proteomic analysis of bile collected from patients with a malignant or benign biliary stenosis (exploratory phase) and (ii) verifying the accuracy of the newly identified potential biomarkers for discriminating malignant versus nonmalignant biliary stenoses in a larger group of patients (confirmation phase). Overall, 66 proteins were found overexpressed (ratio>1.5) in at least one cancer condition using proteomic analysis and 7 proteins were increased in all malignant/nonmalignant disease comparisons. Preliminary screening by immunoblot highlighted carcinoembryonic cell adhesion molecule 6 (CEAM6), a cell surface protein overexpressed in many human cancers, as an interesting candidate biomarker. ELISA subsequently confirmed CEAM6 as a potential bile biomarker for distinguishing malignant from benign biliary stenoses with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.92 (specificity 83%, sensitivity 93%, positive predictive value 93%, and negative predictive value 83%). No significant difference in serum CEAM6 level was found between malignant and nonmalignant samples. Combining bile CEAM6 and serum CA19-9 in a panel further improved diagnostic accuracy for malignant stenoses (AUC 0.96, specificity 83%, sensitivity 97%, positive predictive value 93%, and negative predictive value 91%). CEAM6 measurement in bile could be clinically useful to discriminate between malignant and nonmalignant causes of biliary stenosis. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.
authors.affiliation: Biomedical Proteomics Research Group, Department of Human Protein Sciences, Geneva University, Geneva CH-1211, Switzerland. Electronic address: Annarita.Farina@unige.ch.
authors.forename: Annarita
authors.initials: A
authors.lastname: Farina
authors.affiliation: Division of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva CH-1211, Switzerland.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Dumonceau
authors.affiliation: Biomedical Proteomics Research Group, Department of Human Protein Sciences, Geneva University, Geneva CH-1211, Switzerland.
authors.forename: Paola
authors.initials: P
authors.lastname: Antinori
authors.affiliation: Biomedical Proteomics Research Group, Department of Human Protein Sciences, Geneva University, Geneva CH-1211, Switzerland; Clinical Proteomics Laboratory, Department of Genetic and Laboratory Medicine, Geneva University Hospitals, Geneva CH-1211, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Annessi-Ramseyer
authors.affiliation: Division of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva CH-1211, Switzerland.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Frossard
authors.affiliation: Biomedical Proteomics Research Group, Department of Human Protein Sciences, Geneva University, Geneva CH-1211, Switzerland; Clinical Proteomics Laboratory, Department of Genetic and Laboratory Medicine, Geneva University Hospitals, Geneva CH-1211, Switzerland.
authors.forename: Denis F
authors.initials: DF
authors.lastname: Hochstrasser
authors.affiliation: Department of Gastroenterology, Erasme Hospital, Free University of Brussels, Brussels BE-1070, Belgium.
authors.forename: Myriam
authors.initials: M
authors.lastname: Delhaye
authors.affiliation: Biomedical Proteomics Research Group, Department of Human Protein Sciences, Geneva University, Geneva CH-1211, Switzerland; Clinical Proteomics Laboratory, Department of Genetic and Laboratory Medicine, Geneva University Hospitals, Geneva CH-1211, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lescuyer
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D019540:Area Under Curve; D001650:Bile Duct Neoplasms / Q000150:complications* / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000150:complications / Q000378:metabolism; D002779:Cholestasis / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D012372:ROC Curve
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins
keywords: CEACAM6; Cholangiocarcinoma; NCA-90; Pancreatic cancer; Proteomics; iTRAQ